CN116847927A - Disposable cartridge for reagent storage system and method of using the same - Google Patents

Disposable cartridge for reagent storage system and method of using the same Download PDF

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Publication number
CN116847927A
CN116847927A CN202180085842.XA CN202180085842A CN116847927A CN 116847927 A CN116847927 A CN 116847927A CN 202180085842 A CN202180085842 A CN 202180085842A CN 116847927 A CN116847927 A CN 116847927A
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CN
China
Prior art keywords
seal
cartridge assembly
assembly
chip
biological sample
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Pending
Application number
CN202180085842.XA
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Chinese (zh)
Inventor
卡比尔·山名
迈克尔·尼尔森
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Fumerle International Holdings Ltd
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Fumerle International Holdings Ltd
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Publication of CN116847927A publication Critical patent/CN116847927A/en
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    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B9/00—Piston machines or pumps characterised by the driving or driven means to or from their working members
    • F04B9/02—Piston machines or pumps characterised by the driving or driven means to or from their working members the means being mechanical
    • F04B9/04—Piston machines or pumps characterised by the driving or driven means to or from their working members the means being mechanical the means being cams, eccentrics or pin-and-slot mechanisms
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1003—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
    • C12N15/1006—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers
    • C12N15/1013—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers by using magnetic beads
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/6851—Quantitative amplification
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B43/00—Machines, pumps, or pumping installations having flexible working members
    • F04B43/02—Machines, pumps, or pumping installations having flexible working members having plate-like flexible members, e.g. diaphragms
    • F04B43/04—Pumps having electric drive
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N21/05—Flow-through cuvettes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0668—Trapping microscopic beads
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16—Reagents, handling or storing thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/044—Connecting closures to device or container pierceable, e.g. films, membranes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0654—Lenses; Optical fibres
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0672—Integrated piercing tool
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0883—Serpentine channels
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • B01L2300/123—Flexible; Elastomeric
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/043—Moving fluids with specific forces or mechanical means specific forces magnetic forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0677—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
    • B01L2400/0683—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers mechanically breaking a wall or membrane within a channel or chamber
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B19/00—Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
    • F04B19/006—Micropumps

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Analytical Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Hematology (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Fluid Mechanics (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Mechanical Engineering (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Plant Pathology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)
  • Reciprocating Pumps (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Details Of Reciprocating Pumps (AREA)
  • Degasification And Air Bubble Elimination (AREA)

Abstract

The present application relates generally to a cartridge assembly useful for storing a reagent and a system and method for using the same. Aspects of the present disclosure may include a disposable cartridge assembly for single use only. For example, an exemplary cartridge assembly may include an interlocking feature that can be irreversibly coupled to an assay system (e.g., a chip assembly).

Description

Disposable cartridge for reagent storage system and method of using the same
Cross Reference to Related Applications
The present application is based on the priority benefits of U.S. provisional patent application No. 63/093,640 entitled "Collection Point qPCR System" filed on even date 19 of 10/10 of the year 2020, claim 8 of PCT treaty. The application also relates to PCT application entitled "method and apparatus for controlling fluid volume to achieve separation and PCR amplification", "fluid detection and control algorithm for PCR analysis" and "apparatus with fluid channel geometry for sample-to-result PCR analysis and method of use thereof", and U.S. design application No. 29/812,034 entitled "fluid channel geometry of chip", all filed simultaneously at 2021, 10 and 19, and filed concurrently herewith by the same applicant formula, inc. The contents of the above applications are incorporated herein by reference as if fully set forth herein in their entirety.
Technical Field
The present application relates to reagent storage systems. More specifically, the present disclosure relates to storage systems that can be used to determine, for example, polymerase chain reactions.
Background
Various applications require systems for reagent storage. Several examples of these systems can be found in commercial applications such as the robas Liat platform. The system utilizes a small disposable transfer pipette to move the sample solution from the storage buffer into the reagent storage consumable. Reagents required for performing the assay are sealed in a tube with separate sections. During the assay, specific portions are ruptured to introduce the appropriate reagents at the correct times and in the correct order. This is convenient but requires complex and manual sample handling before the system can be used.
Another approach uses electrowetting with two-phase fluids (such as oil and water/water phases). This approach is commercialized by NuGen (Mondrian), advanced Liquid Logic, illumina (NeoPrep) to keep reagents specific for NGS library construction separate and introduce them in a defined electrowetting sequence.
Both of these methods are suitable for specific applications and have the disadvantage of preventing more general applicability. There remains a need for systems that can be used in automation applications with easier usage and lower cost.
Disclosure of Invention
In general, the present application relates to cartridge assemblies useful for reagent storage and systems and methods for using the same. Aspects of the application may include a disposable cartridge assembly for single use only. For example, an exemplary cartridge assembly may include an interlocking feature that may be irreversibly coupled to an assay system (e.g., a chip assembly). Here, irreversible is intended to mean that the system comprises features that require that the particular will be damaged, destroyed or otherwise be rendered faulty if the cartridge is to be removed from the assay system.
One exemplary aspect of the present disclosure is a system for performing an assay. An exemplary system may include a cartridge assembly and a chip assembly. The cartridge assembly may include: a first surface having a first seal, a second surface having a second seal, and one or more reservoirs located between the first surface and the second surface. The chip assembly may include: a microfluidic channel, and one or more piercing elements configured to pierce the second seal to provide a wet reagent to the chip assembly.
Another exemplary aspect of the disclosure is a method for performing an assay, the method comprising: providing a biological sample to a cartridge assembly; engaging the cartridge assembly with the chip assembly to transfer the biological sample to the chip assembly; moving a biological sample through a microfluidic channel; and exposing the biological sample to a temperature.
Yet another exemplary aspect of the present disclosure is a cartridge assembly for storing wet reagents, the cartridge assembly comprising: a first surface having a first seal, a second surface having a second seal, and one or more reservoirs located between the first surface and the second surface, the reservoirs defining a volume, and wherein at least one of the one or more reservoirs comprises a polymerase.
In particular, the exemplary cassette assemblies, systems, and methods of the present disclosure may be used in applications such as real-time polymerase chain reaction (rtPCR) assays to identify the presence and/or absence of viral RNA based on his or her biological sample to determine the infection status of a patient.
Drawings
Many aspects of the disclosure can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the principles of the present disclosure. Furthermore, in the drawings, like reference numerals designate corresponding parts throughout the several views. In the accompanying drawings
Fig. 1 illustrates an example system including a cartridge assembly and a chip assembly according to an example aspect of the disclosure.
Fig. 2A illustrates an upper perspective view of an exemplary chip assembly in accordance with exemplary aspects of the present disclosure.
Fig. 2B illustrates a lower perspective view of an exemplary chip assembly according to an exemplary aspect of the present disclosure.
Fig. 3 illustrates a top view of an exemplary chip assembly including microfluidic channels according to an exemplary aspect of the present disclosure.
Fig. 4A illustrates an upper perspective view of an exemplary cartridge assembly according to an exemplary aspect of the present disclosure.
Fig. 4B illustrates a lower perspective view of an exemplary cartridge assembly according to an exemplary aspect of the present disclosure.
Fig. 5 illustrates a top view of an exemplary cartridge assembly according to an exemplary aspect of the present disclosure.
Fig. 6A illustrates a side view of an exemplary system for performing an assay prior to engagement of a chip assembly with a cartridge assembly, according to an exemplary aspect of the disclosure.
Fig. 6B illustrates a side view of an exemplary system for performing an assay after a chip assembly is engaged with a cartridge assembly, according to an exemplary aspect of the disclosure.
Fig. 7A illustrates an upper perspective view of an exemplary chip assembly in accordance with exemplary aspects of the present disclosure.
Fig. 7B illustrates a cross-section of an exemplary penetrating member according to an exemplary aspect of the present disclosure.
Detailed Description
The embodiments described herein may be understood more readily by reference to the following detailed description and examples and their previous and following descriptions. However, the elements, devices, and methods described herein are not limited to the specific embodiments presented in the detailed description and examples. It should be understood that these embodiments are merely illustrative of the principles of the present application. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the spirit and scope of the application.
One exemplary embodiment of the present disclosure may include a system for performing an assay. An exemplary system may include a cartridge assembly and a chip assembly having aspects in accordance with examples herein. For example, aspects of the cartridge assembly may include a first surface having a first seal, a second surface having a second seal, and one or more reservoirs between the first surface and the second surface, the reservoirs defining a volume, and at least one of the one or more reservoirs containing a wet reagent. Aspects of the chip assembly may include: a microfluidic channel, and one or more piercing elements configured to pierce the second seal to provide wet reagents to the chip assembly.
Aspects of the first seal may include layers of various materials. For example, in some implementations, the first seal may include a non-reactive layer surrounding one or more reservoirs, and a flexible layer in contact with the non-reactive layer.
Aspects of the second seal may also include layers of various materials. For example, in some implementations, the second seal may include an inert layer surrounding one or more of the reservoirs, and a compressible layer in contact with the inert layer.
Aspects of one or more piercing elements can include a hollow structure. For example, in some implementations, the penetrating element may have a needle structure that allows fluid to flow from the reservoir through the hollow interior of the needle to reach the microfluidic channel.
According to certain implementations, the cartridge assembly and the chip assembly may be oriented such that engaging the cartridge assembly and the chip assembly causes the one or more piercing elements to pierce the second seal and the compressible layer to contact the chip assembly, thereby fluidly sealing the microfluidic channel. For example, the cartridge assembly and the chip assembly may include alignment features such that the cartridge assembly and the chip assembly are oriented such that the penetrating elements on the chip assembly are aligned with the reservoirs. In this way, upon engaging the cartridge assembly and the chip assembly, the piercing element pierces the second seal at the reservoir to provide the wet reagent to the chip assembly.
Additionally, in some implementations, the junction box assembly and the chip assembly may compress the assemblies together to fluidly seal the microfluidic channel. As an illustrative example, the compressible layer may be configured to deform upon engagement of the cartridge assembly and the chip assembly to create a watertight or substantially watertight seal. More specifically, the cartridge assembly and the chip assembly may be oriented such that engaging the cartridge assembly and the chip assembly causes the one or more piercing elements to pierce the second seal and the compressible layer to contact the chip assembly, thereby fluidly sealing the top of the microfluidic channel.
One exemplary aspect of the chip assembly may include an optically transparent encapsulant. For example, some chip assemblies may include an optically transparent seal that forms the bottom of the microfluidic channel. The optically transparent seal may allow for optical detection of material flowing through the microfluidic channel. Thus, according to some example implementations, after the cartridge assembly and the chip assembly are engaged, the microfluidic channel may be fluidly sealed to allow fluid (e.g., sample) to pass through the microfluidic channel.
In some example systems, the cartridge assembly may further include a mechanism configured to prevent engagement of the cartridge assembly with the chip assembly until the mechanism is activated. For example, the mechanism may include a deformable structure that holds the chip assembly and the cartridge assembly apart a distance. Upon application of pressure or other force, the deformable structure may bend or otherwise reduce the distance, thereby bringing the chip assembly and the cartridge assembly into contact.
Another aspect of the exemplary system may include a sample port for providing a biological sample. In these implementations, the sample port may be included on the cartridge assembly, the chip assembly, or both the cartridge assembly and the chip assembly.
In certain implementations, the chip assembly may further include a plurality of metal beads configured to interact with RNA present in the biological sample. One aspect of the plurality of metal beads may include magnetism. Magnetism may include the attraction of a plurality of metal beads to a magnetic field (e.g., the magnetic field of a stationary magnet). For example, in some implementations, the plurality of metal beads may include iron-containing beads, such as steel beads.
Additionally or alternatively, in some implementations, the cartridge assembly may further include one or more one-way snaps configured to engage with portions of the chip. In this way, the splice tray assembly and the chip assembly can have a predetermined pressure and/or distance such that the one-way clasp can engage portions of the chip. This aspect may provide one exemplary option for creating a fluid-tight microfluidic channel. Further, in some implementations, the one-way clasp may include features that irreversibly engage portions of the chip such that the fluid-tight microfluidic channel is not broken once the system is engaged without breaking the system.
Aspects of the exemplary systems of the present disclosure may include assays such as hand-held tests for sample collection, which may then be detected by using different readers. In some implementations of the disclosure, the type of assay may include Polymerase Chain Reaction (PCR). For example, in certain implementations, the one or more reservoirs may include a first reservoir comprising a wash solution and a second reservoir comprising a master mix, wherein the master mix includes at least one polymerase. It should be understood that various polymerases may be used depending on the type of PCR performed. In some implementations, the PCR may be real-time (rtPCR), and the master mix may also include reverse transcriptase for converting RNA to complementary DNA.
One exemplary advantage of an implementation of the present disclosure is a compact and/or commercially viable design. For example, the microfluidic chip may allow for the use of a system comprising wet reagents with a volume in the range of 5 μl to 30 μl (such as 10 μl to 30 μl, 5 μl to 10 μl, or 10 μl to 20 μl).
Another embodiment of the present disclosure includes a method for performing an assay. An example method may include providing a biological sample to a cartridge assembly (e.g., a cartridge assembly as described herein). For example, the cartridge assembly may include: a first surface having a first seal, a second surface having a second seal, and one or more reservoirs located between the first surface and the second surface, the reservoirs defining a volume, and wherein at least one of the one or more reservoirs contains a wet reagent.
The example method may further include engaging a cartridge assembly with a chip assembly (e.g., a chip assembly as described herein) to transfer the biological sample to the chip assembly. For example, the chip assembly may include: a microfluidic channel, and one or more piercing elements configured to pierce the second seal to provide wet reagents to the chip assembly.
The example method may further include moving the biological sample through the microfluidic channel.
One aspect of the exemplary method may include engaging the cartridge assembly with the chip assembly to fluidly connect one or more reservoirs of the cartridge assembly with a microfluidic channel of the chip assembly.
In some methods, moving the biological sample through the microfluidic channel may include: pressure is applied to one or more regions of the first seal whereby the pressure is fluidly transferred to the biological sample.
Another aspect of certain methods may include lysing the biological sample. As an illustrative example, in some methods, after engaging the cartridge assembly with the chip assembly, the wet reagent is mixed with the biological sample to produce a liquid biological sample.
Another aspect of certain methods may include exposing the biological sample to a temperature. For example, in some methods, the microfluidic channel may comprise: a first serpentine maintained at a first temperature, a second serpentine maintained at a second temperature, and a detection volume between the first and second serpentine, wherein the second temperature is different from the first temperature. In these implementations, moving the biological sample through the microfluidic channel may include: fluid flow is induced by applying pressure to at least one region of the first seal, wherein the fluid flow directionally moves the biological sample from the first serpentine region to the detection volume and the second serpentine region. In addition, reversing the fluid flow by removing pressure to at least one region of the first seal, by applying pressure to another region of the first seal, or both, the other region of the first seal being different from the at least one region of the first seal, and wherein reversing the fluid flow causes the biological sample to directionally move from the second serpentine region to the detection volume and the first serpentine region.
Thus, in general, an exemplary method for performing an assay may comprise: the biological sample is exposed to a first temperature, the biological sample is exposed to a second temperature, and the process is repeated. In an exemplary implementation, the temperature cycling is illustrated by flowing a fluid containing a biological sample through a first region of a microfluidic channel maintained at a first temperature to a second region of the microfluidic channel maintained at a second temperature. The flow direction is then reversed, transferring the fluid to the first region of the microfluidic channel. The method may be performed using an exemplary microfluidic channel as disclosed herein. For example, the microfluidic channel may be a continuous channel having a first serpentine region, a subsequent detection volume, and a subsequent second serpentine region, wherein the first and second serpentine regions are separately located on the chip assembly and the detection volume separates the locations of the first and second serpentine regions.
For certain exemplary methods of the present disclosure, making an assay may also include iteratively repeating the fluid flow and reversing the fluid flow for a plurality of cycles. The process of repeatedly exposing a biological sample to a first temperature and a second temperature may also be referred to as temperature cycling, which may be used to perform certain assays.
Some implementations of the present disclosure may include detection-based assays for qualitative and/or quantitative screening. For example, aspects of certain methods may include detecting a signal from a biological sample, wherein detecting the signal is performed while moving the biological sample through a microfluidic channel. Some exemplary signals may include luminescence profiles from fluorescent probes and/or colored probes.
Aspects of certain implementations of the disclosure may include methods and/or systems for performing Polymerase Chain Reaction (PCR). In some implementations, the cartridge assembly (e.g., one or more reservoirs) may include wet reagents for PCR, such as a master mix including at least one polymerase. Other exemplary wet reagents may include washes, buffers, pH adjusters, lysis compositions, or other PCR reagents.
Another embodiment of the present disclosure may include a kit assembly for storing wet reagents. An exemplary cartridge assembly may include: a first surface having a first seal, a second surface having a second seal, and one or more reservoirs located between the first surface and the second surface, the reservoirs defining a volume, and wherein at least one of the one or more reservoirs comprises a polymerase.
Aspects of a cartridge assembly according to the present disclosure may include a first seal and a second seal that provide a top and a bottom, respectively, that enclose a volume defined by a reservoir.
For implementations of the present disclosure, the first seal may include a non-reactive layer facing the one or more reservoirs, and a compressible layer adhered to the non-reactive layer.
Additionally or alternatively, the second seal may include an inert layer facing the one or more reservoirs, and a flexible layer in contact with the inert layer.
More specifically, according to some implementations of the present disclosure, the inert layer, the non-reactive layer, or both the inert layer and the non-reactive layer may include: metal foil (e.g., aluminum foil), fluorinated polymer (e.g., polytetrafluoroethylene), or a combination thereof.
The application will be better understood with reference to the following non-limiting examples and embodiments and with reference to the foregoing drawings.
Examples
This embodiment shows some implementations according to the present disclosure. These examples are not meant to limit the embodiments to only those examples herein, but are used to illustrate some of the possible implementations.
An exemplary system with a chip assembly and a cartridge assembly was produced according to the following design specifications:
the chip and cartridge are assembled in irreversible steps.
A plurality of puncture-resistant features are included to prevent the chip from prematurely puncturing the wet reagent reservoir.
Once the cartridge is placed in the assay reader instrument and ready for the assay, the puncture resistant feature moves/changes.
A user operated port is included for adding a sample swab and then sealing the sample swab.
Orienting the chip and cartridge such that the instrument compresses the chip into the cartridge causes sharp features on the chip to pierce the bottom of the cartridge in each reservoir to effect a subsequent assay, and
the entire consumable remains sealed for measurement and can then be discarded after measurement.
The cartridge assembly includes the following features: the elastomeric foil seal closest to the wet agent for chemical compatibility, and a layer of rubber. At the top of the box, the rubber layer acts as a pressure membrane that stretches and deforms under the pin. Once the chip is engaged with the cartridge, the rubber layer acts as a gasket material to form a solid seal between the cartridge and the chip at the bottom of the cartridge.
The chip assembly includes the following features: the fluid channel on one side is fluidly connected to the piercing pin on the top of the chip. Once the chips are pressed together into the box, the pins push through the rubber and foil seals. The flexible rubber may form a seal on the pin as the primary seal. There is a raised ring on the chip that also serves to form a second seal against the rubber in the event of a bad or incomplete seal on the pins.
Referring to fig. 1, this figure shows the orientation of elements that together form a system including a cartridge assembly and a chip assembly. Fig. 1 includes the following elements: a flexible layer (top), a non-reactive layer (second from top), a cartridge comprising a reservoir (third from top), a sample port and a cap for the sample port, an inert layer (fourth from top) and a compressible layer (fifth from top). The first five elements together form an exemplary cartridge assembly. Fig. 1 also includes the following elements: a chip (sixth from the top) and a bottom seal (bottom) adhered to the chip. The last two elements together form an exemplary chip assembly.
In the example shown, a flexible layer on top of the chip, attached to a non-reactive layer (fifth from the top), may be used as a membrane for moving the contained liquid. Additionally, the compressible layer may be used to fluidly seal the cartridge to the chip once the cartridge assembly and the chip assembly are engaged. The fluid reservoir on the cartridge itself is open at both ends, the top of the reservoir being wide enough to deform the rubber membrane into its pressed against the pins, and the bottom containing a hole slightly larger than the piercing feature on the chip. The hole is sealed in its original state. In addition, the sample may be sealed for a cartridge assembly including a connection cap.
Referring to fig. 2A, a top perspective view of an exemplary chip assembly is depicted showing a plurality of piercing elements surrounded by a sealing feature that can be used to reduce loss of substance transferred from a reservoir after the reservoir is pierced. Fig. 2B depicts a bottom perspective view of the exemplary chip assembly of fig. 2A. The microfluidic channel of fig. 2B is fluidly connected to the lancing element of fig. 2A such that fluid from the reservoir is transferred from the reservoir to the microfluidic channel after engagement with the cartridge assembly. For example, the piercing element may be hollow such that fluid in the reservoir passes through the piercing element to the region of the microfluidic channel below the piercing element.
Referring to fig. 3, an exemplary microfluidic channel design is depicted. The microfluidic channel may comprise a plurality of serpentine regions, a plurality of entry points for fluids contained in the reservoir of the cartridge assembly, at least one filter, at least one burst valve (channel constriction), and an optical detection region.
Referring to fig. 4A, an upper perspective view of an exemplary cartridge assembly is depicted. At the top, the cartridge assembly may include a port for insertion of a biological sample. The cartridge assembly may also include one or more reservoirs, which may include a fluid (e.g., a solution) containing the assay components. Fig. 4B illustrates a bottom perspective view of the exemplary cartridge assembly of fig. 4A. Fig. 4B shows the bottom feature of the reservoir (represented by concentric circles). Fig. 4B also depicts one possible design of a one-way snap for holding a chip on a cartridge. The lower flexible catch on the cartridge assembly can engage the chip assembly and hold the system together after it is initially assembled in the factory until the assay is performed. A retention catch may be included to hold the chip assembly against the chip stop feature. The chip stop feature may be designed to hold the chip assembly at a distance from the cartridge assembly to prevent the piercing feature on the chip from prematurely piercing the bottom seal on the cartridge. Some or all of these features together may be used to maintain an orientation between the chip assembly and the cartridge assembly such that engaging both assemblies results in a biological sample being provided to the microfluidic channel.
Referring to fig. 5, a top view of an exemplary cartridge assembly is depicted. The figure shows 4 reservoirs (features shown as two concentric circles), a waste outlet (which discharges waste fluid into the waste area), a release (for unlocking the chip during a transition from the first configuration shown in fig. 6A to the second configuration shown in fig. 6B), and a sample port with a capping feature. A steering handle is also shown to allow a user to easily grasp and steer the case.
Referring to fig. 6A, a cross-section of a system including a cartridge assembly oriented above a chip assembly is depicted. The cartridge assembly and the chip assembly are held in place by chip stop features (e.g., upper snaps, lower snaps). Fig. 6B depicts a cross-section of the system of fig. 6A after the cartridge assembly and the chip assembly are engaged. Once the two components are engaged, the piercing feature on the chip pierces the seal on the bottom of the reservoir. Gravity or pressure applied to the top seal/membrane of the reservoir may cause the fluid contained in the reservoir to flow to the microfluidic channel.
Referring to fig. 7A, a top perspective view of an alternative chip including a plurality of lancing elements is depicted. Fig. 7B depicts a cross-section of an exemplary lancing element, the exemplary lancing element showing a hollow internal structure that allows fluid communication between a reservoir of a cartridge and a channel of a chip. A light catch tray is provided around each piercing element to capture and retain any fluid leakage.
Description of the embodiments
Some additional, non-limiting, exemplary embodiments are provided below.
Embodiment 1. A system for performing detection, comprising:
a cartridge assembly, wherein the cartridge assembly comprises:
a first surface having a first seal,
a second surface having a second seal, and
one or more reservoirs located between the first surface and the second surface, the reservoirs defining a volume, and wherein at least one of the one or more reservoirs contains a wet reagent; and
a chip assembly, wherein the chip assembly comprises:
microfluidic channel, and
one or more lancing elements configured to pierce the second seal to provide the wet reagent to the chip assembly.
Embodiment 2. The system of embodiment 1, wherein the first seal comprises:
a non-reactive layer surrounding the one or more reservoirs, and
a flexible layer in contact with the non-reactive layer.
Embodiment 3. The system of embodiment 2, wherein the second seal comprises:
an inert layer surrounding the one or more reservoirs, and
a compressible layer in contact with the inert layer.
Embodiment 4. The system of embodiment 3, wherein the cartridge assembly and the chip assembly are oriented such that engaging the cartridge assembly and the chip assembly causes the one or more piercing elements to pierce the second seal and the compressible layer to contact the chip assembly to fluidly seal the microfluidic channel.
Embodiment 5. The system of embodiment 1, wherein the chip assembly further comprises an optically transparent seal, and wherein the optically transparent seal forms a bottom of the microfluidic channel.
Embodiment 6. The system of embodiment 5, wherein the cartridge assembly and the chip assembly are oriented such that engaging the cartridge assembly and the chip assembly causes the one or more piercing elements to pierce the second seal and the compressible layer to contact the chip assembly to fluidly seal the top of the microfluidic channel.
Embodiment 7. The system of embodiment 1, wherein the cartridge assembly further comprises a mechanism configured to prevent engagement of the cartridge assembly with the chip assembly until the mechanism is activated.
Embodiment 8. The system of embodiment 1, wherein the cartridge assembly and/or the chip assembly further comprises a sample port for providing a biological sample.
Embodiment 9. The system of embodiment 8, wherein the chip assembly further comprises a plurality of metal beads configured to interact with RNA present in the biological sample.
Embodiment 10. The system of embodiment 1, wherein the cartridge assembly further comprises one or more one-way snaps configured to irreversibly engage with portions of the chip.
Embodiment 11. The system of embodiment 1, wherein the one or more reservoirs comprise: a first reservoir comprising a wash solution and a second reservoir comprising a master mix, wherein the master mix comprises at least one polymerase.
Embodiment 12. The system of embodiment 1, wherein the assay comprises a Polymerase Chain Reaction (PCR).
Embodiment 13. The system of embodiment 1, wherein the volume is 5 μl to 30 μl.
Embodiment 14. A method for performing detection, the method comprising:
providing a biological sample to a cartridge assembly, wherein the cartridge assembly comprises:
a first surface having a first seal,
a second surface having a second seal, and
one or more reservoirs located between the first surface and the second surface, the reservoirs defining a volume, and wherein at least one of the one or more reservoirs contains a wet reagent;
engaging the cartridge assembly with a chip assembly to transfer the biological sample to the chip assembly, wherein the chip assembly comprises:
microfluidic channel, and
one or more lancing elements configured to pierce the second seal to provide the wet reagent to the chip assembly; and
moving the biological sample through the microfluidic channel, wherein
After engaging the cartridge assembly with the chip assembly, the one or more reservoirs become fluidly connected to the microfluidic channel.
Embodiment 15. The method of embodiment 14, wherein moving the biological sample through the microfluidic channel comprises:
pressure is applied to one or more regions of the first seal, whereby the pressure is fluidly transferred to the biological sample.
Embodiment 16. The method of embodiment 14, wherein, after engaging the cartridge assembly with the chip assembly, the wet reagent is mixed with the biological sample to produce a liquid biological sample.
Embodiment 17. The method of embodiment 15, the microfluidic channel comprising: a first serpentine maintained at a first temperature, a second serpentine maintained at a second temperature, and a detection volume between the first and second serpentine, wherein the second temperature is different from the first temperature, and wherein moving the biological sample through the microfluidic channel comprises:
inducing a fluid flow by applying pressure to at least one region of the first seal, wherein the fluid flow directionally moves the biological sample from the first serpentine region to the detection volume and the second serpentine region; and
reversing the fluid flow by removing pressure to the at least one region of the first seal, by applying pressure to another region of the first seal, or both, wherein the other region of the first seal is different from the at least one region of the first seal, and wherein reversing the fluid flow causes the biological sample to directionally move from the second serpentine region to the detection volume and the first serpentine region.
Embodiment 18. The method of embodiment 17, further comprising: the fluid flow will be caused and the fluid flow will be reversed iteratively repeated for a plurality of cycles.
Embodiment 19. The method of embodiment 14, further comprising:
detecting a signal from the biological sample, wherein the detection of the signal is performed while moving the biological sample through the microfluidic channel.
Embodiment 20. The method of embodiment 14, wherein the one or more reservoirs comprise: a first reservoir comprising a wash solution and a second reservoir comprising a master mix, wherein the master mix comprises at least one polymerase.
Embodiment 21. The method of embodiment 14, wherein the determining comprises Polymerase Chain Reaction (PCR).
Embodiment 22. The method of embodiment 14, wherein the volume is 5 μl to 30 μl.
Embodiment 23. A cartridge assembly for storing wet reagents, wherein the cartridge assembly comprises:
a first surface having a first seal,
a second surface having a second seal, and
one or more reservoirs located between the first surface and the second surface, the reservoirs defining a volume, and wherein at least one of the one or more reservoirs comprises a polymerase.
Embodiment 24. The cartridge assembly of embodiment 23, wherein the first seal and the second seal provide a top and a bottom, respectively, that enclose the volume defined by the reservoir.
Embodiment 25. The cartridge assembly of embodiment 23, wherein the first seal comprises a non-reactive layer facing the one or more reservoirs, and a compressible layer adhered to the non-reactive layer.
Embodiment 26. The cartridge assembly of embodiment 25, wherein the second seal comprises an inert layer facing the one or more reservoirs, and a flexible layer in contact with the inert layer.
Embodiment 27. The cartridge assembly of embodiment 26, wherein the inert layer, the non-reactive layer, or both the inert layer and the non-reactive layer comprise: metal foil, fluorinated polymer, or combinations thereof.
Embodiment 28. The cartridge assembly of embodiment 27, wherein the fluorinated polymer is polytetrafluoroethylene.
The terms "comprising," including, "" containing, "" having, "and variations thereof mean" including but not limited to.
The term "consisting of … …" means "including and limited to".
The term "consisting essentially of … …" means that a composition, method, or structure may include additional ingredients, steps, and/or portions, but only if the additional ingredients, steps, and/or portions do not materially alter the basic and novel characteristics of the claimed composition, method, or structure.
The term "plurality" means "two or more".
As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, the term "compound" or "at least one compound" may include a plurality of compounds, including mixtures thereof.
Throughout the present application, various embodiments of the application may be presented in a range format. It should be understood that the description of the range format is merely for convenience and brevity and should not be interpreted as inflexible limitation on the scope of the application. Accordingly, the description of a range should be considered to have specifically disclosed all possible sub-ranges as well as individual values within the range. For example, a range description such as 1 to 6 should be considered to have specifically disclosed sub-ranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as individual numbers within that range, e.g., 1, 2, 3, 4, 5, and 6. This applies regardless of the width of the range.
Whenever a range of values is referred to herein, it is intended to include any of the recited numbers (fractional or integer) within the indicated range. The phrases "coverage/range between a first indicator number and a second indicator number" and "coverage/range from a first indicator number" to a second indicator number "are used interchangeably herein and are meant to include the first indicator number and the second indicator number and all fractions and integers therebetween.
It is appreciated that certain features of the application, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the application which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable features in any other described embodiment of the application. Certain features described in the context of various embodiments should not be considered as essential features of those embodiments unless the embodiment is not functional without those elements.
While the application has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, the present application is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.
All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. Furthermore, the citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present application. Where segment headers are used, they should not be construed as necessarily limiting.

Claims (28)

1. A system for performing an assay, comprising:
a cartridge assembly, wherein the cartridge assembly comprises:
a first surface having a first seal,
a second surface having a second seal, and
one or more reservoirs located on the first surface and the first surface
Between the two surfaces, the reservoir defines a volume, and wherein the
At least one of the one or more reservoirs contains a wet reagent; and
a chip assembly, wherein the chip assembly comprises:
microfluidic channel, and
one or more piercing elements configured to pierce
Penetrating the second seal to provide the wet test to the chip assembly
And (3) an agent.
2. The system of claim 1, wherein the first seal comprises:
a non-reactive layer surrounding the one or more reservoirs, and
a flexible layer in contact with the non-reactive layer.
3. The system of claim 2, wherein the second seal comprises:
an inert layer surrounding the one or more reservoirs, and
a compressible layer in contact with the inert layer.
4. The system of claim 3, wherein the cartridge assembly and the chip assembly are oriented such that engaging the cartridge assembly and the chip assembly causes the one or more piercing elements to pierce the second seal and the compressible layer to contact the chip assembly to fluidly seal the microfluidic channel.
5. The system of claim 1, wherein the chip assembly further comprises an optically transparent seal, and wherein the optically transparent seal forms a bottom of the microfluidic channel.
6. The system of claim 5, wherein the cartridge assembly and the chip assembly are oriented such that engaging the cartridge assembly and the chip assembly causes the one or more piercing elements to pierce the second seal and the compressible layer to contact the chip assembly to fluidly seal the top of the microfluidic channel.
7. The system of claim 1, wherein the cartridge assembly further comprises a mechanism configured to prevent engagement of the cartridge assembly with the chip assembly until the mechanism is activated.
8. The system of claim 1, wherein the cartridge assembly and/or the chip assembly further comprises a sample port for providing a biological sample.
9. The system of claim 8, wherein the chip assembly further comprises a plurality of metal beads configured to interact with RNA present in the biological sample.
10. The system of claim 1, wherein the cartridge assembly further comprises one or more one-way snaps configured to irreversibly engage with portions of the chip.
11. The system of claim 1, wherein the one or more reservoirs comprise:
a first reservoir comprising a wash solution and a second reservoir comprising a master mix, wherein the master mix comprises at least one polymerase.
12. The system of claim 1, wherein the assay comprises a Polymerase Chain Reaction (PCR).
13. The system of claim 1, wherein the volume is 5 μl to 30 μl.
14. A method for performing an assay, the method comprising:
providing a biological sample to a cartridge assembly, wherein the cartridge assembly comprises:
a first surface having a first seal,
a second surface having a second seal, and
one or more reservoirs located on the first surface and the first surface
Between the two surfaces, the reservoir defines a volume, and wherein the
At least one of the one or more reservoirs contains a wet reagent;
engaging the cartridge assembly with a chip assembly to transfer the biological sample to the chip assembly, wherein the chip assembly comprises:
microfluidic channel, and
one or more piercing elements configured to pierce
The second seal to provide the wet reagent to the chip assembly;
and
moving the biological sample through the microfluidic channel, wherein,
after engaging the cartridge assembly with the chip assembly, the one or more reservoirs become fluidly connected to the microfluidic channel.
15. The method of claim 14, wherein moving the biological sample through the microfluidic channel comprises:
pressure is applied to one or more regions of the first seal, whereby the pressure is fluidly transferred to the biological sample.
16. The method of claim 14, wherein the wet reagent mixes with the biological sample to produce a liquid biological sample after the cartridge assembly is engaged with the chip assembly.
17. The method of claim 15, wherein the microfluidic channel comprises: a first serpentine maintained at a first temperature, a second serpentine maintained at a second temperature, and a detection volume between the first and second serpentine, wherein the second temperature is different from the first temperature, and wherein moving the biological sample through the microfluidic channel comprises:
inducing a fluid flow by applying pressure to at least one region of the first seal, wherein the fluid flow directionally moves the biological sample from the first serpentine region to the detection volume and the second serpentine region; and
reversing the fluid flow by removing pressure to the at least one region of the first seal, by applying pressure to another region of the first seal, or both, wherein the other region of the first seal is different from the at least one region of the first seal, and wherein reversing the fluid flow causes the biological sample to directionally move from the second serpentine region to the detection volume and the first serpentine region.
18. The method of claim 17, further comprising: the fluid flow will be caused and the fluid flow will be reversed iteratively repeated for a plurality of cycles.
19. The method of claim 14, further comprising:
detecting a signal from the biological sample, wherein the detection of the signal is performed while moving the biological sample through the microfluidic channel.
20. The method of claim 14, wherein the one or more reservoirs comprise:
a first reservoir comprising a wash solution and a second reservoir comprising a master mix, wherein the master mix comprises at least one polymerase.
21. The method of claim 14, wherein the determining comprises Polymerase Chain Reaction (PCR).
22. The method of claim 14, wherein the volume is 5 μl to 30 μl.
23. A cartridge assembly for storing wet reagents, wherein the cartridge assembly comprises:
a first surface having a first seal,
a second surface having a second seal, and
one or more reservoirs located between the first surface and the second surface, the reservoirs defining a volume, and wherein at least one of the one or more reservoirs comprises a polymerase.
24. The cartridge assembly of claim 23, wherein the first and second seals provide a top and bottom, respectively, that encloses the volume defined by the reservoir.
25. The cartridge assembly of claim 23, wherein the first seal comprises a non-reactive layer facing the one or more reservoirs, and a compressible layer adhered to the non-reactive layer.
26. The cartridge assembly of claim 25, wherein the second seal comprises an inert layer facing the one or more reservoirs, and a flexible layer in contact with the inert layer.
27. The cartridge assembly of claim 26, wherein the inert layer, the non-reactive layer, or both the inert layer and the non-reactive layer comprise: metal foil, fluorinated polymer, or combinations thereof.
28. The cartridge assembly of claim 27, wherein the fluorinated polymer is polytetrafluoroethylene.
CN202180085842.XA 2020-10-19 2021-10-19 Disposable cartridge for reagent storage system and method of using the same Pending CN116847927A (en)

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